‘Gene drive’ tool can prevent epidemics

The genetically engineered mosquitoes now living in a Southern California basement lab, secured behind five locked doors, prove that it may be possible to wipe out malaria.

Now we must decide whether or not we should do it.

A new technology called “gene drive” makes it possible — for the first time in history — to alter an entire population by changing the laws of evolution, eliminating insect-borne infectious diseases.

On the horizon are creatures that are not only incapable of transmitting malaria, but also are unable to spread diseases such as dengue fever, which kills tens of thousands of children every year. Or Bubonic plague, yellow fever, West Nile virus, Lyme disease and countless other infectious scourges.

But the approach has triggered a debate that has become so contentious that many bioethicists urge hitting the “pause” button on testing and release of these insects, until greater safeguards and oversight are established.

“Using gene drive vastly multiplies our power to change the genomes of species around the world, whether domesticated or wild,” said Hank Greely, director of Stanford’s Center for Law and the Biosciences.

“Our current regulatory system does not seem capable of ensuring that these kinds of changes get any oversight, let alone the kind of careful review needed,” he said. “It needs attention now.”

MALARIA RESISTANT GENE

The newly engineered mosquitoes, unveiled this past week by UC Irvine scientists in the journal Proceedings of the National Academy of Sciences, carry a malaria-resistant gene taken from mice. Using gene drive, the gene was passed onto 99 percent of the offspring. In the wild, scientists say, the inserted gene could take over an entire population in a single season. And the gene was protective, successfully fending off the malaria parasite.

The finding was the culmination of 20 years of research by UC Irvine geneticist Anthony James, who collaborated with a team led by geneticist Ethan Bier of UC San Diego. They are urging that the mosquitoes quickly be released into the wild and are looking for a community willing to volunteer.

The scientists’ approach, which enlists the gene-editing tool called CRISPR, breaks the rules of evolution: While a typical gene has only a 50-50 chance of being passed from a parent to a offspring’s chromosome, gene drive copies a gene onto both of the offspring’s chromosomes. This pattern of inheritance means a trait passes onto future generations at twice the normal rate.

If that alteration inhibits reproduction or survival in some way, gene drive could drive a population into extinction.

This week, the debate over gene editing will move onto the international stage with the prestigious National Academy of Sciences holding a summit in Washington D.C. to guide its use in humans. On Dec. 7 and 8, it will debate gene editing in animals — including insects.

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DEATH TOLL CLIMBS

If these modified mosquitoes are released, they could transform public health. Malaria alone kills more than 650,000 people each year, most of them children, while afflicting 200 million more with debilitating fevers.

“Compare this approach to (spraying) pesticides like DDT,” said Arthur Caplan, director of the Division of Medical Ethics at NYU Langone Medical Center. “Or bed nets, which don’t work. We’ve tried different drugs, but they haven’t proven to be good preventatives.

“I’m willing to trade off mosquitoes for a huge burden of human disease” and economic productivity lost to disease, Caplan added. “I’m not sure anybody cares that much about them. ... They’re just one big pest.”

Gene drive tools could enable us to address other problems in global health, agriculture and ecology, experts say. For instance, it might be possible to reverse pesticide and herbicide resistances in insects and weeds. It could help control invasive species, which cause more than $40 billion in damages to U.S. agriculture every year.

At the same time, there is emerging concern over our ability to accurately predict the ecological and human consequences of this intervention — which could persist forever in future generations. Altering an entire population, or eliminating it altogether, could have drastic and unknown impact. Other pests might emerge to fill an ecological void. Or useful predators higher up the food chain might suffer. If it mutates, it could create unpredictable effects.

NATIVE OF INDIA

The Irvine mosquitoes are native to urban India, not California. So if they escaped, they would likely perish in California’s climate. But ecologists fear: What if other engineered species escape, survive and then breed with natural populations?

Before these insects are released, there needs to be a foolproof “off switch,” experts say. In an effort to create such safeguards, Harvard scientist George Church is pioneering a method to reverse the changes created by gene drive.

Moreover, experts say, a better regulatory system is needed to monitor their impact.

“It is essential that national regulatory authorities and international organizations get on top of this — really get on top of this,” according to Kenneth Oye, a political scientist at the Massachusetts Institute of Technology who wrote a commentary in the journal Science.

The new mosquito falls into the overlap area of three federal agencies: the Food and Drug Administration, the Department of Agriculture and the Environmental Protection Agency, Greely said.

The FDA might consider the new genetic construct an “animal drug,” but it doesn’t govern mosquitoes. The USDA’s Animal Welfare Act protects species, but the mosquito isn’t one of them. The EPA might seek a role, if entire native populations are altered.

“Overall, we have three agencies and multiple statutes coming into play,” wrote Greely and University of Wisconsin law professor Alta Charo in an upcoming issue of the journal American Journal of Bioethics. “This might be reassuring, but it also may mean there will be a morass each time a critter seems to fall between the cracks.”

And because insects cross national boundaries, it is important to review the international agreements that regulate the release and global spread of engineered creatures, said Eleonore Pauwels of the Science and Technology Innovation Program at the Woodrow Wilson International Center for Scholars in Washington, D.C.

The tiny Irvine mosquitoes are a big wake-up call, she said.

“What happened in the basement of the Irvine campus brings us to a new technological and ecological frontier,” Pauwels said.

“Acknowledging that gene drive technologies might help us face public health crises,” she said, “we need to care for and improve them.”